Autoantibodies directed against the insulin receptor are an uncommon cause of severe insulin resistant dibetes mellitus. Autoantibodies and insulin compete with each other for binding to many cell types. Both insulin and one of these antibodies induce negatively cooperative site-site interactions. Like insulin, insulin competable antibody binding was saturable. The spontaneous dissociation of both prebound insulin and antibody were pH-dependent, although that of insulin was more sensitive. These anti-receptor autoantibodies possess extraordinary insulin-like characteristics, competing with insulin for receptor binding and stimulating receptor mediated responses apparently by similar mehanisms to insulin itself.